AU2020240075A1 - Methods of producing bioconjugates of e. coli o-antigen polysaccharides, compositions thereof, and methods of use thereof - Google Patents
Methods of producing bioconjugates of e. coli o-antigen polysaccharides, compositions thereof, and methods of use thereof Download PDFInfo
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Families Citing this family (8)
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RU2711512C2 (ru) | 2013-01-17 | 2020-01-17 | Экс4 Фамасьютиклз (Остриэ) ГмбХ | Рекомбинантное антитело, фармацевтический препарат, диагностический препарат, способ идентификации антитела-кандидата, способ лечения, профилактики и способ диагностики субъектов, потенциально подверженных риску заражения или страдающих от инфекций, вызванных штаммами Е. coli с множественной лекарственной устойчивостью |
CN106535927B (zh) | 2014-02-24 | 2019-09-20 | 葛兰素史密丝克莱恩生物有限公司 | 新颖多糖及其用途 |
TWI715617B (zh) | 2015-08-24 | 2021-01-11 | 比利時商葛蘭素史密斯克藍生物品公司 | 對抗腸道外病原性大腸桿菌之免疫保護之方法及組合物 |
AR109621A1 (es) | 2016-10-24 | 2018-12-26 | Janssen Pharmaceuticals Inc | Formulaciones de vacunas contra glucoconjugados de expec |
WO2020191082A1 (fr) | 2019-03-18 | 2020-09-24 | Janssen Pharmaceuticals, Inc. | Bioconjugués d'antigènes polysaccharidiques o d'e. coli, procédés de production de ces derniers, et méthodes d'utilisation de ces derniers |
MX2023003169A (es) * | 2020-09-17 | 2023-03-27 | Janssen Pharmaceuticals Inc | Composiciones de vacunas multivalentes y usos de las mismas. |
IL301880A (en) | 2020-11-30 | 2023-06-01 | Janssen Pharmaceuticals Inc | Analytical method for glycoconjugation using a capillary-based immunoassay system |
JP2024513914A (ja) | 2021-04-08 | 2024-03-27 | ヤンセン ファーマシューティカルズ,インコーポレーテッド | バイオコンジュゲート生産のためのプロセス |
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US3700612A (en) | 1971-06-23 | 1972-10-24 | Tenneco Chem | Aqueous surface-coating compositions containing hydroxyalkyl ethers of galactomannan gums as thickeners |
US5057540A (en) | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
US4912094B1 (en) | 1988-06-29 | 1994-02-15 | Ribi Immunochem Research Inc. | Modified lipopolysaccharides and process of preparation |
US5370872A (en) | 1991-08-12 | 1994-12-06 | Swiss Serum And Vaccine Institute Berne | Escherichia coliO-polysaccharide-protein conjugate vaccine |
PT761231E (pt) | 1992-06-25 | 2000-06-30 | Smithkline Beecham Biolog | Composicao de vacina contendo adjuvantes |
CA2284586C (fr) | 1997-04-01 | 2011-02-08 | Ribi Immunochem Research, Inc. | Compositions d'adjuvant immunologique aqueuses de monophosphoryle lipide a |
US6491919B2 (en) | 1997-04-01 | 2002-12-10 | Corixa Corporation | Aqueous immunologic adjuvant compostions of monophosphoryl lipid A |
DK1126876T3 (da) | 1998-10-16 | 2007-07-02 | Glaxosmithkline Biolog Sa | Adjuvanssystemer og vacciner |
AU5162201A (en) | 2000-04-13 | 2001-10-30 | Corixa Corporation | Immunostimulant compositions comprising an aminoalkyl glucosaminide phosphate and qs-21 |
US6676958B2 (en) | 2001-06-19 | 2004-01-13 | Advanced Bioadjuvants, Llc | Adjuvant composition for mucosal and injection delivered vaccines |
DE60303591T2 (de) | 2002-03-07 | 2007-03-01 | Eidgenössische Technische Hochschule Zürich | System und methode zur herstellung von rekombinanten, glykosylierten protein in prokaryontischen wirtszellen |
CN1324134C (zh) * | 2003-12-22 | 2007-07-04 | 南开大学 | 对大肠杆菌o81型的o-抗原特异的核苷酸 |
ATE483027T1 (de) | 2005-05-11 | 2010-10-15 | Eth Zuerich | Rekombinante n-glykosylierte proteine aus prokaryontischen zellen |
TWI457133B (zh) | 2005-12-13 | 2014-10-21 | Glaxosmithkline Biolog Sa | 新穎組合物 |
ES2536426T3 (es) | 2006-03-23 | 2015-05-25 | Novartis Ag | Compuestos de imidazoquinoxalina como inmunomoduladores |
US8063063B2 (en) | 2006-03-23 | 2011-11-22 | Novartis Ag | Immunopotentiating compounds |
EP2242505A4 (fr) | 2008-01-08 | 2012-03-07 | Biogenerix Ag | Glycoconjugaison de polypeptides employant des oligosaccharyltransférases |
JP5782258B2 (ja) | 2008-02-20 | 2015-09-24 | グリコヴァキシン アーゲー | 原核細胞由来の組換えn−グリコシル化タンパク質から作製したバイオコンジュゲート |
CN102481312B (zh) | 2009-06-05 | 2015-07-15 | 传染性疾病研究院 | 合成的吡喃葡萄糖脂佐剂 |
CN102724997B (zh) | 2009-11-19 | 2016-09-21 | 格林考瓦因有限公司 | 在原核细胞中产生免疫原性多糖的生物合成系统 |
CN103391714A (zh) | 2010-12-10 | 2013-11-13 | 默沙东公司 | 减轻搅动引起的免疫原性组合物聚集的新制剂 |
JP2014526449A (ja) | 2011-09-06 | 2014-10-06 | グリコヴァキシン アーゲー | 原核細胞において製造されるバイオコンジュゲートワクチン |
US9932598B2 (en) | 2012-08-02 | 2018-04-03 | The Regents Of The University Of California | Metabolic engineering of microbial organisms |
BR112015004817A2 (pt) | 2012-09-10 | 2017-07-04 | Glycovaxyn Ag | bioconjugados compreendendo antígenos modificados e seus usos |
ES2905107T3 (es) | 2012-10-12 | 2022-04-07 | Glaxosmithkline Biologicals Sa | Procedimientos de modificación de células hospedadoras |
EP2917351B1 (fr) * | 2012-11-07 | 2018-12-19 | GlaxoSmithKline Biologicals S.A. | Production d'un vaccin recombinant dans e. coli par conjugaison enzymatique |
JP2016501550A (ja) | 2012-12-27 | 2016-01-21 | グリコヴァキシン アーゲー | Crm197に関する方法及び組成物 |
RU2711512C2 (ru) | 2013-01-17 | 2020-01-17 | Экс4 Фамасьютиклз (Остриэ) ГмбХ | Рекомбинантное антитело, фармацевтический препарат, диагностический препарат, способ идентификации антитела-кандидата, способ лечения, профилактики и способ диагностики субъектов, потенциально подверженных риску заражения или страдающих от инфекций, вызванных штаммами Е. coli с множественной лекарственной устойчивостью |
LT2996473T (lt) | 2013-05-18 | 2019-12-10 | Aduro Biotech Inc | Kompozicijos ir būdai, skirti aktyvuoti nuo "interferono geno stimuliatoriaus" priklausomą signalinį kelią |
CA2926523C (fr) | 2013-10-11 | 2023-09-26 | Glycovaxyn Ag | Methodes de modification de cellule hote |
EP2870974A1 (fr) * | 2013-11-08 | 2015-05-13 | Novartis AG | Vaccins conjugués de salmonelle |
JP2016540764A (ja) | 2013-12-04 | 2016-12-28 | グリコヴァキシン アーゲー | 大腸菌で合成された糖タンパク質ワクチンによる黄色ブドウ球菌感染の予防 |
CA2935532A1 (fr) | 2014-02-06 | 2015-08-13 | Arsanis Biosciences Gmbh | Sequences d'anticorps specifiques diriges contre e. coli |
CN106535927B (zh) | 2014-02-24 | 2019-09-20 | 葛兰素史密丝克莱恩生物有限公司 | 新颖多糖及其用途 |
ES2805000T3 (es) | 2014-04-17 | 2021-02-10 | Glaxosmithkline Biologicals Sa | Células huéspedes modificadas y usos de las mismas |
CN105695497B (zh) | 2014-11-27 | 2019-09-24 | 中国人民解放军军事医学科学院生物工程研究所 | 一种细菌多糖修饰的重组融合蛋白的制备方法及其应用 |
EP3240895B1 (fr) | 2014-12-30 | 2022-01-26 | GlaxoSmithKline Biologicals S.A. | Compositions et methodes pour la glycosylation de proteine |
TWI715617B (zh) | 2015-08-24 | 2021-01-11 | 比利時商葛蘭素史密斯克藍生物品公司 | 對抗腸道外病原性大腸桿菌之免疫保護之方法及組合物 |
GB201518668D0 (en) | 2015-10-21 | 2015-12-02 | Glaxosmithkline Biolog Sa | Immunogenic Comosition |
GB201610599D0 (en) | 2016-06-17 | 2016-08-03 | Glaxosmithkline Biologicals Sa | Immunogenic Composition |
AR109621A1 (es) | 2016-10-24 | 2018-12-26 | Janssen Pharmaceuticals Inc | Formulaciones de vacunas contra glucoconjugados de expec |
GB201721582D0 (en) * | 2017-12-21 | 2018-02-07 | Glaxosmithkline Biologicals Sa | S aureus antigens and immunogenic compositions |
WO2020191082A1 (fr) | 2019-03-18 | 2020-09-24 | Janssen Pharmaceuticals, Inc. | Bioconjugués d'antigènes polysaccharidiques o d'e. coli, procédés de production de ces derniers, et méthodes d'utilisation de ces derniers |
FR3098334B1 (fr) | 2019-07-05 | 2021-07-23 | Airbus Operations Sas | Procédé et système de surveillance d’un état de conscience d’un opérateur dans un poste de pilotage d’un aéronef |
MX2023003169A (es) | 2020-09-17 | 2023-03-27 | Janssen Pharmaceuticals Inc | Composiciones de vacunas multivalentes y usos de las mismas. |
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CN113950524A (zh) | 2022-01-18 |
HRP20231026T1 (hr) | 2023-12-08 |
MA55365B1 (fr) | 2023-09-27 |
BR112021018258A2 (pt) | 2022-02-08 |
JP2022525773A (ja) | 2022-05-19 |
EP3942028C0 (fr) | 2023-06-07 |
PL3942028T3 (pl) | 2023-10-23 |
KR102574882B1 (ko) | 2023-09-04 |
EP3942028B1 (fr) | 2023-06-07 |
EP4253554A3 (fr) | 2024-01-17 |
MD3942028T2 (ro) | 2023-11-30 |
TWI771663B (zh) | 2022-07-21 |
WO2020191088A9 (fr) | 2021-03-18 |
MA55365A (fr) | 2022-01-26 |
EP3942028A1 (fr) | 2022-01-26 |
EP4253554A2 (fr) | 2023-10-04 |
MX2021011418A (es) | 2021-10-13 |
US20230190926A1 (en) | 2023-06-22 |
US20200353073A1 (en) | 2020-11-12 |
HUE063875T2 (hu) | 2024-02-28 |
WO2020191088A1 (fr) | 2020-09-24 |
AU2020240075A8 (en) | 2021-10-21 |
KR20210134044A (ko) | 2021-11-08 |
TW202102670A (zh) | 2021-01-16 |
RS64521B1 (sr) | 2023-09-29 |
CA3134045A1 (fr) | 2020-09-24 |
SG11202110303XA (en) | 2021-10-28 |
ES2951442T3 (es) | 2023-10-20 |
IL286467A (en) | 2021-12-01 |
EA202192392A1 (ru) | 2022-02-09 |
EP3942028B9 (fr) | 2023-08-23 |
AR118389A1 (es) | 2021-09-29 |
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